Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease

Chest. 2015 Jun;147(6):1549-1557. doi: 10.1378/chest.14-0631.

Abstract

Background: Human telomere disease consists of a wide spectrum of disorders, including pulmonary, hepatic, and bone marrow abnormalities. The extent of bone marrow and liver abnormalities in patients with interstitial lung disease (ILD) and short telomeres is unknown.

Methods: The lung transplant clinic established a prospective protocol to identify short telomeres in patients with ILD not related to connective tissue disease or sarcoidosis. Patients with short telomeres underwent bone marrow biopsies, liver biopsies, or both as part of the evaluation for transplant candidacy.

Results: One hundred twenty-seven patients met ILD categorization for inclusion. Thirty were suspected to have short telomeres, and 15 had the diagnosis confirmed. Eight of 13 (53%) patients had bone marrow abnormalities. Four patients had hypocellular marrow associated with macrocytosis and relatively normal blood counts, which resulted in changes to planned immunosuppression at the time of transplant. Four patients with more severe hematologic abnormalities were not listed because of myelodysplastic syndrome (two); monoclonal gammopathy of unclear significance (one); and hypocellular marrow, decreased megakaryocyte lineage associated with thrombocytopenia (one). Seven patients underwent liver biopsies, and six had abnormal liver pathology. These abnormalities did not affect listing for lung transplant, and liver biopsies are no longer routinely obtained.

Conclusions: Subclinical bone marrow and liver abnormalities can be seen in patients with ILD and short telomeres, in some cases in the absence of clinically significant abnormalities in peripheral blood counts and liver function tests. A larger study examining the implication of these findings on the outcome of patients with ILD and short telomeres is needed.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy
  • Blood Cell Count
  • Bone Marrow / pathology*
  • Cohort Studies
  • Female
  • Humans
  • Liver / pathology*
  • Liver Function Tests
  • Lung Diseases, Interstitial / blood
  • Lung Diseases, Interstitial / pathology*
  • Lung Transplantation
  • Male
  • Middle Aged
  • Mutation / genetics
  • Patient Selection
  • Prospective Studies
  • Retrospective Studies
  • Telomerase / genetics
  • Telomere / enzymology*
  • Telomere / genetics
  • Telomere / pathology*

Substances

  • Telomerase